New combination antiretroviral therapies have demonstrated unprecedented efficacy yet require strict adherence to complex dosing regimens to inhibit rapid virus replication and the generation of multi-drug resistant strains. The proposed project for a FIRST TIME R01 is a randomized, controlled intervention to enhance antiretroviral adherence among an inner city group of many current or former injection drug users -- a population at high risk of nonadherence. The study site is Jacobi Medical Center's AIDS Consultation Services in the Bronx, New York, where attending physicians will be working in collaboration with the PI. The intervention involves a peer support or "buddy" system that is practical, inexpensive, does not require extensive training or additional staff, and has the potential for widespread dissemination. Drawing on the social support literature and social learning theory, the intervention is designed to provide affirmational, emotional, spiritual, and informational support to target three key groups of factors that have been empirically demonstrated to affect adherence: self- efficacy, negative affective states, and knowledge of the medication regimen. Clinic staff will employ specific criteria to nominate patients as "buddies." They will undergo a 6-session training and be supervised and supported thereafter in a facilitated support group. The buddies will then be assigned to 75 patient "peers." The buddies will provide social support via thrice weekly phone calls and visits for 3-months in accordance with a protocol explained and rehearsed in their training. Adherence of these patients and 75 patients in a treatment-as-usual control condition from the same clinic population will be assessed with self-reports, 3-day recall telephone interviews at months 2 and 4, and the Medication Event Monitoring System (MEMS). All participants will be administered self-report inventories (assessing demographics and other potential moderators, social support, adherence, as well as the factors purported to relate to adherence) at baseline, at the end of the 3-month intervention, and at a 3-month follow-up. In addition to potentially demonstrating empirically the feasibility and efficacy of a peer support intervention, this study will expand current knowledge about the correlates of adherence in this population. Such knowledge has implications for the design of future interventions and clinical trials, where adequate adherence is necessary to insure the validity and reliability of findings regarding new HIV therapies.